A5101919168- Pharmacogenetics and Drug Metabolism
- Hormonal Regulation and Hypertension
- Estrogen and related hormone effects
- Drug Transport and Resistance Mechanisms
- Cholesterol and Lipid Metabolism
- Receptor Mechanisms and Signaling
- Pancreatic and Hepatic Oncology Research
- Ubiquitin and proteasome pathways
- Multiple Myeloma Research and Treatments
- Liver Disease Diagnosis and Treatment
- Cancer, Hypoxia, and Metabolism
- Porphyrin Metabolism and Disorders
- Advanced Glycation End Products research
- Protein Degradation and Inhibitors
- PI3K/AKT/mTOR signaling in cancer
- Folate and B Vitamins Research
- Cancer-related gene regulation
- Chronic Kidney Disease and Diabetes
- Metabolism, Diabetes, and Cancer
- Acute Kidney Injury Research
- Tea Polyphenols and Effects
- Piperaceae Chemical and Biological Studies
- Zebrafish Biomedical Research Applications
- Bone and Joint Diseases
- Innovative Educational Techniques
National Clinical Research Center for Digestive Diseases
2025
Air Force Medical University
2025
Xijing Hospital
2025
Xi'an Jiaotong University
2025
Zhejiang Chinese Medical University
2024
St. Jude Children's Research Hospital
2013-2023
Guizhou Provincial People's Hospital
2015-2021
Guizhou University
2006-2018
Guangzhou Medical University
2017
Guangzhou First People's Hospital
2017
Low to moderate consumption of red wine reportedly has a relatively greater benefit than other alcoholic beverages in the prevention atherosclerosis and coronary heart disease (CHD). This beneficial effect is increasingly attributed polyphenol resveratrol, present wine. In study, we investigated effects resveratrol on aggregation platelets isolated from healthy, normotensive male volunteers rabbits with experimental hypercholesterolemia. Platelet rate (PAR) was measured using Born's method....
Abstract Many drugs bind to and activate human pregnane X receptor (hPXR) upregulate drug-metabolizing enzymes, resulting in decreased drug efficacy increased resistance. This suggests that hPXR antagonists have therapeutic value. Here we report SPA70 is a potent selective antagonist. inhibits hepatocytes humanized mouse models enhances the chemosensitivity of cancer cells, consistent with role Unexpectedly, SJB7, close analog SPA70, an agonist. X-ray crystallography reveals SJB7 resides...
Abstract Background The expression of the drug-metabolizing enzyme cytochrome P450 3A4 (CYP3A4) is regulated by pregnane × receptor (PXR), which modulated numerous signaling pathways, including cyclin-dependent kinase (Cdk) pathway. Flavonoids, commonly consumed humans as dietary constituents, have been shown to modulate various pathways (e.g., inhibiting Cdks). Flavonoids also induce CYPs expression, but underlying mechanism action unknown. Here, we report responsible for flavonoid-mediated...
The 48 human nuclear receptors (NRs) form a superfamily of transcription factors that regulate major physiological and pathological processes. Emerging evidence suggests NR crosstalk can fundamentally change our understanding biology, but detailed molecular mechanisms are lacking. Here, we report the basis between pregnane X receptor (PXR) constitutive androstane (CAR), where they novel heterodimer, resulting in their mutual inhibition. PXR CAR drug metabolism energy metabolism. Although...
Constitutive androstane receptor (CAR) and pregnane X (PXR) are xenobiotic sensors that enhance the detoxification elimination of xenobiotics endobiotics by modulating expression genes encoding drug-metabolizing enzymes transporters. Elevated levels efflux transporters, resulting from CAR activation in various cancers, promote chemotherapeutic agents, leading to reduced therapeutic effectiveness acquired drug resistance. inhibitors, combination with existing chemotherapeutics, could...
We previously reported a specific inverse agonist (SPA70) of the nuclear receptor pregnane X (PXR). However, derivatization SPA70 yielded only agonists and neutral antagonists, suggesting that agonism PXR is difficult to achieve. Therefore, we sought design proteolysis targeting chimeras (PROTACs) aimed at inducing degradation. Conjugation derivative ligands E3 substrate cereblon (CRBN) resulted in one molecule, SJPYT-195, reduced protein level an optimized degradation assay described here....
Hepatocellular carcinoma (HCC) is a well-known inflammation-related cancer, that accounts for fifth most prevalent neoplasm and the third major driver of cancer associated fatality globally. Accumulating evidence has elucidated C-X-C motif chemokine ligands (CXCLs) are aberrantly upregulated in HCC involved inflammation-induced hepatocarcinogenesis metastasis. Herein, we identified novel function DEAD-box RNA helicase 17 (DDX17) as an oncogenic factor via transactivating CXCL8 HCC. Unlike...
Background/Objectives: Nestin is an intermediate filament protein and a marker of odontoblasts, but its function in tooth bone formation largely unknown. This study aimed to determine whether plays role postnatal formation. Methods: 4-week-old knockout (KO) mice were analyzed with range techniques, including X-ray imaging, uCT, backscattered acid-etched casted SEM, FITC-confocal microscopy, H&E TRAP staining, immunohistochemistry. Results: The KO had no apparent difference crown compared...
In a mouse model, rifampicin and isoniazid combination treatment results in cholestatic liver injury that is associated with an increase protoporphyrin IX, the penultimate heme precursor.Both ferrochelatase (FECH/Fech) aminolevulinic acid synthase 1 (ALAS1/Alas1) are crucial enzymes regulating biosynthesis.Isoniazid has recently been reported to upregulate Alas1 but downregulate Fech protein levels mice; however, mechanism by which mediates disruption of synthesis unclear.Two metabolites...
The human pregnane X receptor (PXR) regulates genes involved in drug metabolism and disposition. PXR associates with multiple corepressors that attenuate coactivators enhance its activity. plays a vital role the pathway, comprehensive examination of PXR-associated proteins will provide greater insight into regulation possible therapeutic implications. We performed mass spectrometric screen to identify proteins. Here we report tumor suppressor protein p53 can associate downregulate A...
The xenobiotic receptors pregnane X receptor (PXR) and constitutive androstane (CAR) are activated by structurally diverse chemicals to regulate the expression of target genes, they have overlapping regulation in terms ligands genes. Receptor-selective agonists are, therefore, critical for studying function PXR CAR. An early effort identified 6-(4-chlorophenyl)imidazo[2,1-b][1,3]thiazole-5-carbaldehyde-O-(3,4-dichlorobenzyl)oxime (CITCO) as a selective human CAR (hCAR) agonist, this has...
Pregnane X receptor (PXR) plays roles in detoxification and other physiological processes. PXR activation may enhance drug metabolism (leading to adverse reactions) or inhibit inflammation. Therefore, agonists, antagonists, inverse agonists serve as research tools candidates. However, a specific modulator with an associated structure–activity relationship is lacking. Based on the scaffold of human (hPXR) antagonist SPA70 (10), we developed 81 analogs evaluated their receptor-binding cellular...
This study aims to develop an instrument measure infectious disease specialist nurses' core competence and examining the scale's validity reliability.With increase of diseases, more attention has been paid nursing care. The nurses is directly related quality work. In previous researches, was measured by tools developed for general instead specialized tools, which made it difficult clarify in diseases department.Preliminary items were through literature review, theoretical research,...
The locomotive action involves diverse coordination, necessitating the integration of multiple motor neural circuits. However, precise circuitry mechanism governing emotion-driven accelerated locomotion remains predominantly elusive. Here we dissect projections from tuberomammillary nucleus (TMN) to subiculum (SUB) which promote alert-driven locomotion. We find that TMN histaminergic neurons respond high-speed in both natural and alert acceleration. TMN-SUB circuit is sufficient but not...
Human pregnane X receptor (hPXR) is a nuclear that regulates the expression of phase I and II drug-metabolism enzymes, as well drug transporters. hPXR "xenobiotics sensor" can be activated by structurally diverse compounds. The activation its agonists increases clearance xenobiotics increasing enzymes transporters, possibly leading to toxicity, resistance, other adverse reactions. Therefore, antagonists might attenuate agonist-mediated reduce risk Several have been reported, but none them...
The pregnane X receptor (PXR) is a key regulator of drug metabolism. Many drugs bind to and activate PXR, causing adverse responses. This suggests that PXR inhibitors have therapeutic value, but potent so far been lacking. Herein, we report the structural optimization series 1H-1,2,3-triazole-4-carboxamides compounds led discovery compound 85 as selective most inverse agonist antagonist with low nanomolar IC50 values for binding cellular activity. Importantly, 89, close analog 85, pure study...